Aromatic L-amino acid decarboxylase inhibitor

An aromatic L-amino acid decarboxylase inhibitor (AADC inhibitor) is a type of drug that inhibits the enzyme aromatic L-amino acid decarboxylase (AADC). This enzyme is responsible for the decarboxylation of aromatic L-amino acids, such as L-DOPA, into their corresponding amines, such as dopamine. AADC inhibitors are used in combination with L-DOPA in the treatment of Parkinson's disease to prevent the peripheral conversion of L-DOPA to dopamine, thereby increasing the availability of L-DOPA to the central nervous system.

Levodopa pathway

Mechanism of Action

Aromatic L-amino acid decarboxylase inhibitors work by binding to the AADC enzyme and inhibiting its activity. This prevents the conversion of L-DOPA to dopamine outside the brain. Since dopamine cannot cross the blood-brain barrier, inhibiting its peripheral synthesis ensures that more L-DOPA is available to enter the brain, where it can be converted to dopamine by the AADC enzyme present in the central nervous system.

Clinical Use

AADC inhibitors are primarily used in the management of Parkinson's disease. They are administered in combination with L-DOPA, the precursor to dopamine, to enhance its efficacy. By preventing the peripheral conversion of L-DOPA to dopamine, AADC inhibitors reduce the side effects associated with peripheral dopamine, such as nausea and cardiovascular effects.

Common AADC Inhibitors

• Carbidopa - Often combined with L-DOPA in medications such as Sinemet.
• Benserazide - Used in combination with L-DOPA in medications like Madopar.

Pharmacokinetics

AADC inhibitors do not cross the blood-brain barrier, which is why they selectively inhibit peripheral AADC activity. This selective inhibition is crucial for their therapeutic effect, as it allows for increased central availability of L-DOPA without affecting the central conversion of L-DOPA to dopamine.

Side Effects

The use of AADC inhibitors can lead to side effects, although these are generally related to the increased levels of L-DOPA. Common side effects include:

• Nausea
• Orthostatic hypotension
• Dyskinesias

Related Pages

• Parkinson's disease
• Dopamine
• L-DOPA
• Blood-brain barrier

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